Intermediates for pyridyl-thiazoles and their use to protect plants against infections by micro-organisms

ABSTRACT

New pyridyl-thiazoles of the formula and new intermediates of the formulae in which all variables have the meaning given in the description. All compounds and their salts and acid adducts are suitable for the protection of plants against attack by undesirable microorganisms.

This application is a divisional of application Ser. No. 08/952,353,filed on Nov. 19, 1997 (now U.S. Pat. No. 5,945,380); which is a 371 ofPCT/EP96/02052, filed on May 14, 1996.

The present invention relates to new pyridyl-thiazoles, severalprocesses for their preparation and their use for protecting plantsagainst attack by undesirable microorganisms.

It has already been disclosed that certain halogenopyridine-4-carboxylicacid derivatives can be employed for generating resistance in plantsagainst attack by phytopathogenic microorganisms (cf. EP-OS (EuropeanPublished Specification) 0 268 775 and DE-OS (German PublishedSpecification) 4 138 026). Thus, for example,2,6-dichloropyridine-4-carboxylic acid, methyl2,6-dichloropyridine-4-carboxylate and α-(4-chlorophenyl)-benzyl2,6-dichloropyridine-4-carboxylate can be used for the purposementioned. However, the action of these substances is not alwayssatisfactory, above all when low amounts are applied. Furthermore, thedirect fungicidal action of these compounds leaves something to bedesired.

New pyridyl-thiazoles of the formula ##STR3## in which R representsalkyl, ##STR4## wherein R¹ represents hydrogen or --CO--R⁵,

R² represents hydrogen or --CO--R⁶,

R³ represents hydrogen or alkyl,

R⁴ represents alkoxy or dialkylamino,

R⁵ and R⁶ independently of one another represent alkyl, alkoxycarbonyl,alkylamino, optionally substituted aryl, optionally substitutedarylamino or optionally substituted arylsulphonylamino, or

R¹ and R², together with the nitrogen atom to which they are bonded,represent a cyclic imide of the formula ##STR5## wherein A representsoptionally substituted alkanediyl or optionally substituted alkenediyl,

X¹ represents hydrogen or halogen and

X² represents halogen,

and salts and acid adducts thereof have now been found.

It has furthermore been found that pyridyl-thiazoles of the formula (I)and salts and acid adducts thereof are obtained by a process in which

a) halogenoacetyl-pyridines of the formula ##STR6## in which X¹ and X²have the abovementioned meanings and

X³ represents halogen,

are reacted with thio compounds of the formula ##STR7## in which R hasthe abovementioned meaning,

if appropriate in the presence of a diluent and if appropriate in thepresence of an acid-binding agent, or

b) aminothiazoles of the formula ##STR8## in which X¹ and X² have theabovementioned meanings, are reacted either

α) with carboxylic anhydrides of the formulae ##STR9## in which R⁵ hasthe abovementioned meaning or ##STR10## in which A has theabovementioned meaning, or

β) with carboxylic halides of the formula ##STR11## in which R⁵ has theabovementioned meaning and

X⁴ represents halogen, or

γ) with isocyanates of the formula

    R.sup.7 --N═C═O                                    (VII)

in which

R⁷ represents alkyl, optionally substituted aryl or optionallysubstituted arylsulphonyl, or

δ) with acetals of the formula ##STR12## in which R³ and R⁴ have theabovementioned meanings and

R⁸ represents alkyl,

if appropriate in the presence of a diluent, if appropriate in thepresence of a catalyst and if appropriate in the presence of anacid-binding agent,

and, if appropriate, the compounds of the formula (I) thus obtained arethen reacted with an acid or base.

Finally, it has been found that the pyridyl-thiazoles of the formula (I)and salts and acid adducts thereof can be used particularly suitably forprotecting plants against attack by undesirable microorganisms. Thesubstances according to the invention are suitable both for generatingresistance in plants against attack by undesirable microorganisms and asmicrobicides for combating the microorganisms directly.

Surprisingly, the substances according to the invention are moresuitable for generating resistance in plants against attack byphytopathogenic microorganisms than 2,6-dichloro-pyridine-4-carboxylicacid, methyl 2,6-dichloro-pyridine-4-carboxylate andα-(4-chlorophenyl)-benzyl 2,6-dichloro-pyridine-4-carboxylate, which arestructurally similar compounds which are already known from the priorart and have the same type of action. Furthermore, the substancesaccording to the invention surprisingly are also superior in respect oftheir fungicidal activity to the substances already described which arestructurally the most similar.

Where appropriate, the substances according to the invention can be inthe form of mixtures of various possible isomeric forms, such as, forexample, in the form of stereoisomers or tautomers. The inventionrelates both to stereoisomers and to tautomers, and also to any desiredmixtures of these isomers.

Formula (I) provides a general definition of the pyridyi-thiazolesaccording to the invention.

R preferably represents straight-chain or branched alkyl having 1 to 6carbon atoms or the groups ##STR13## R¹ also preferably representshydrogen or --CO--R⁵. R² also preferably represents hydrogen or--CO--R⁶.

R³ preferably represents hydrogen or straight-chain or branched alkylhaving 1 to 4 carbon atoms.

R⁴ represents alkoxy having 1 to 4 carbon atoms, or representsdialkylamino having 1 to 4 carbon atoms in each alkyl group.

R⁵ and R⁶ independently of one another preferably representstraight-chain or branched alkyl having 1 to 6 carbon atoms,alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy group,alkylamino having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms,arylamino having 6 to 10 carbon atoms or arylsulphonylamino having 6 to10 carbon atoms, it being possible for each of the three latter radicalsto be mono- to trisubstituted in the aryl part in an identical ordifferent manner by halogen, cyano, nitro, formyl, carboxyl, carbamoyl,alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms,alkylthio having 1 to 6 carbon atoms, alkylsulphinyl having 1 to 4carbon atoms, alkylsulphonyl having 1 to 4 carbon atoms, halogenoalkylhaving 1 to 4 carbon atoms and 1 to 5 fluorine, chlorine and/or bromineatoms, halogenoalkoxy having 1 to 4 carbon atoms and 1 to 5 fluorine,chlorine and/or bromine atoms, halogenoalkylthio having 1 to 4 carbonatoms and 1 to 5 fluorine, chlorine and/or bromine atoms,halogenoalkylsulphinyl having 1 to 4 carbon atoms and 1 to 5 fluorine,chlorine and/or bromine atoms, halogenoalkylsulphonyl having 1 to 4carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms,alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy part,hydroximinoalkyl having 1 to 4 carbon atoms in the alkyl part,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy part and 1 to 4carbon atoms in the alkyl part and/or divalent alkanediyl having 3 or 4carbon atoms, in which one or two (non-adjacent) carbon atoms can bereplaced by oxygen and in which the alkanediyl part can be mono- totetrasubstituted in an identical or different manner by halogen, alkylhaving 1 to 4 carbon atoms and/or halogenoalkyl having 1 or 2 carbonatoms and 1 to 3 fluorine, chlorine and/or bromine atoms.

R¹ and R² furthermore, together with the nitrogen atom to which they arebonded, represent a cyclic imide of the formula ##STR14## A preferablyrepresents alkanediyl having 2 or 3 carbon atoms or alkenediyl having 2or 3 carbon atoms, it being possible for the radicals mentioned in eachcase to be mono- to tetrasubstituted in an identical or different mannerby halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4carbon atoms, halogenoalkyl having, 1 to 4 carbon atoms and 1 to 5fluorine, chlorine and/or bromine atoms and/or halogenoalkoxy having 1to 4 carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms.

X¹ preferably represents hydrogen, fluorine, chlorine or bromine.

X² preferably represents fluorine, chlorine or bromine.

R particularly preferably represents methyl, ethyl, n-propyl, isopropyl,n-butyl, sec-butyl, iso-butyl, tert-butyl or the groups ##STR15## R¹also particularly preferably represents hydrogen or --CO--R⁵. R² alsoparticularly preferably represents hydrogen or --CO--R⁶.

R³ particularly preferably represents hydrogen, methyl or ethyl.

R⁴ particularly preferably represents methoxy, ethoxy, dimethylamino ordiethylamino.

R⁵ and R⁶ independently of one another particularly preferably representmethyl, ethyl n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl,tert-butyl, methoxycarbonyl, ethoxycarbonyl, methylamino, ethylamino,n-propylamino, isopropylamino, n-butylamino, sec-butylamino,iso-butylamino, tert-butylamino, phenyl, naphthyl, phenylamino,naphthylamino, phenylsulphonylamino or naphthylsulphonylamino, it beingpossible for each of the six latter radicals to be mono- totrisubstituted in the aryl part in an identical or different manner byfluorine, chlorine, bromine, cyano, nitro, formyl, carboxyl, carbamoyl,methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy,n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio,methylsulphinyl, ethylsulphinyl, methylsulphonyl or ethylsulphonyl,trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy,difluorochloromethoxy, trifluoroethoxy, difluoromethylthio,difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulphinylor trifluoromethylsulphonyl, methoxycarbonyl, hydroximinomethyl,hydroximinoethyl, methoximinomethyl, ethoximinomethyl, methoximinoethylor ethoximinoethyl and/or by in each case divalent trimethylene(propane-1,3-diyl), methylenedioxy or ethylenedioxy, in each caseoptionally mono- to tetrasubstituted in an identical or different mannerby fluorine, chlorine, methyl, trifluoromethyl, ethyl or n- or i-propyl.

R¹ and R² furthermore, together with the nitrogen atom to which they arebonded, represent a cyclic imide of the formula ##STR16## A particularlypreferably represents alkanediyl having 2 or 3 carbon atoms oralkenediyl having 2 or 3 carbon atoms, it being possible for theradicals mentioned in each case to be mono- to trisubstituted in anidentical or different manner by fluorine, chlorine, bromine, cyano,methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy,n- or i-propoxy, trifluoromethyl, trifluoroethyl, difluoromethoxy,trifluoromethoxy, difluorochloromethoxy and/or trifluoroethoxy.

X¹ particularly preferably represents hydrogen, fluorine or chlorine.

X² particularly preferably represents fluorine or chlorine.

The definitions of radicals mentioned generally above or mentioned inthe preferred ranges apply both to the end products of the formula (I)and accordingly to the particular starting substances or intermediateproducts required for the preparation.

These definitions of radicals can be combined with one another asdesired, that is to say also between the stated ranges of preferredcompounds.

Preferred compounds according to the invention are also salts which areobtainable by reaction of pyridyl-thiazoles of the formula ##STR17## inwhich R⁶, X¹ and X² have the abovementioned meanings,

with strong bases of the formula

    HOMe                                                       (IX)

in which

Me represents an alkali metal ion, one equivalent of an alkaline earthmetal ion, an ammonium ion, an alkylammonium ion having 1 to 4 carbonatoms, a dialkylammonium ion having 1 to 4 carbon atoms in each alkylgroup or a trialkylammonium ion having 1 to 4 carbon atoms in each alkylgroup.

Particularly preferred such salts of pyridyl-thiazoles of the formula(Ib) are those in which R⁶, X¹ and X² have the meanings given above asparticularly preferred and Me represents a lithium, sodium or potassiumion, or represents one equivalent of a magnesium, calcium, strontium orbarium ion, or represents an ammonium, methylammonium, ethylammonium,dimethylammonium, diethylammonium, trimethylammonium or triethylammoniumion.

Preferred substances according to the invention are also additionproducts of acids and those pyridyl-thiazoles of the formula (I) inwhich X¹, X² and R have the meanings given above as preferred.

The acids which can be added on include, preferably, hydrohalic acids,such as, for example, hydrochloric acid and hydrobromic acid, inparticular hydrochloric acid, and furthermore phosphoric acid, nitricacid, sulphuric acid, mono- and bifunctional carboxylic acids andhydroxycarboxylic acids, such as, for example, acetic acid, maleic acid,succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid,sorbic acid and lactic acid, as well as sulphonic acids, such as, forexample, p-toluenesulphonic acid, 1,5-naphthalenedisulphonic acid orcamphorsulphonic acid, saccharin and thiosaccharin.

If 4-bromoacetyl-2,6-dichloro-pyridine and thiourea are used as startingsubstances, the course of process (a) according to the invention can beillustrated by the following equation: ##STR18##

If [4-(2,6-dichloro-pyridin-4-yl)-thiazol-2-yl]-amine and aceticanhydride are used as starting substances, the course of process b),variant (α) according to the invention can be illustrated by thefollowing equation: ##STR19##

If [4-(2,6-dichloro-pyridin-4-yl)-thiazol-2-yl]-amine and2-trifluoromethyl-phenyl-sulphonyl isocyanate are used as startingsubstances, the course of process (b), variant (γ) according to theinvention can be illustrated by the following equation: ##STR20##

IfN-[4-(2,6-dichloro-pyridin-4-yl)-thiazol-2-yl]-N'-(2-trifluoromethyl-phenyl-sulphonyl)-ureais used as the starting substance and sodium hydroxide is used as thereaction component, the preparation of salts by the process according tothe in vention can be illustrated by the following equation. ##STR21##

The abovementioned salt can also exist in the tautomeric form having thestructure ##STR22##

Formula (II) provides a general definition of thehalogenoacetylpyridines required as starting substances for carrying outprocess (a) according to the invention. In this formula (II) X¹ and X²preferably have those meanings which have already been mentioned aspreferred for X¹ and X² in connection with the description of thecompounds of the formula (I) according to the invention. X³ preferablyrepresents chlorine or bromine.

Some of the halogenoacetyl-pyridines of the formula (II) are known (cf.DE-A 1 811 833).

The halogenoacetyl-pyridines of the formula ##STR23## in which X²represents halogen,

X⁵ represents halogen and

X⁶ represents chlorine, bromine or iodine,

are new.

Formula (IIa) provides a general definition of the newhalogenoacetyl-pyridines.

X² preferably represents fluorine, chlorine or bromine.

X⁵ preferably represents fluorine, chlorine or bromine.

X⁶ preferably represents chlorine or bromine.

Particularly preferred halogenoacetyl-pyridines of the formula (IIa) arethose in which

X² represents fluorine or chlorine,

X⁵ represents fluorine or chlorine and

X⁶ represents chlorine or bromine.

The new halogenoacetyl-pyridines of the formula (IIa) can be prepared by

c) reacting acetylpyridines of the formula ##STR24## in which X² and X⁵have the abovementioned meanings,

with halogenating agents, if appropriate in the presence of a diluentand if appropriate in the presence of a catalyst.

The known halogenoacetyl-pyridines of the formula (II) can be preparedin an an alogous manner.

If 4-acetyl-2,6-dichloro-pyridine is used as the starting substance andbromine is used as the halogenating agent, the course of process (c) canbe illustrated by the following equation. ##STR25##

Formula (X) provides a general definition of the acetylpyridinesrequired as starting substances in carrying out process (c). In thisformula X² and X⁵ preferably have those meanings which have already beenmentioned as preferred for these radicals in connection with thedescription of th e compounds of the formula (IIa).

The acetylpyridines of the formula (X) were hitherto still unknown. Theycan be prepared by

d) reacting malonic ester derivatives of the formula ##STR26## in whichX² and X⁵ have the abovementioned meanings,

R⁹ represents alkyl and

R¹⁰ represents alkyl,

with water, if appropriate in the presence of a diluent.

If dimethyl 2,6-dichloro-iso-nicotinoyl-malonate is used as the startingsubstance and water is used as the reaction component, the course ofprocess (d) can be illustrated by the following equation. ##STR27##

In a special variant, process (d) can also be carried out by onlyeffecting a partial hydrolysis and decarboxylation. The esters resultingin this way of the formula ##STR28## X², X⁵ and R⁹ have theabovementioned meanings, can be isolated and then reacted in a furtherstage under the reaction conditions of process (d) to giveacetylpyridines of the formula (X).

Formula (XI) provides a general definition of the malonic estersrequired as starting substances in carrying out process (d). In thisformula X² and X⁵ preferably have those meanings which have already beenmentioned as preferred for these radicals in connection with thedescription of the compounds of the formula (IIa). R⁹ preferablyrepresents alkyl having 1 to 6 carbon atoms, particularly preferablymethyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl ortert-butyl. R¹⁰ likewise preferably represents alkyl having 1 to 6carbon atoms, particularly preferably methyl, ethyl, n-propyl,isopropyl, n-butyl, iso-butyl, sec-butyl or tert-butyl.

The malonic ester derivatives of the formula (XI) were hitherto stillunknown. They can be prepared by

e) reacting isonicotinoyl halides of the formula ##STR29## in which X²and X⁵ have the abovementioned meanings and

X⁷ represents halogen,

with malonic esters of the formula ##STR30## in which R⁹ and R¹⁰ havethe abovementioned meanings,

if appropriate in the presence of a diluent, and also if appropriate inthe presence of an acid binding agent, and if appropriate in thepresence of a catalyst.

The malonic ester derivatives of the formula (XI) and also their saltsand acid adducts are very highly suitable for the protection of plantsagainst attack by undesirable microorganisms.

If 2,6-dichloro-isonicotinoyl chloride is used as the starting substanceand dimethyl malonate as the reaction component, the course of process(e) can be illustrated by the following equation. ##STR31##

The malonic ester derivatives of the formula (XI) in general exist inthe form of tautomer mixtures which can be characterized by thefollowing formulae: ##STR32##

Formula (XIII) provides a general definition of the isonicotinoylhalides required as starting substances in carrying out process (e). Inthis formula X² and X⁵ preferably have those meanings which have alreadybeen mentioned as preferred for these radicals in connection with thedescription of the compounds of the formula (IIa). X⁷ preferablyrepresents chlorine.

The isonicotinoyl halides of the formula (XIII) are known or can beprepared by processes which are known in principle (cf. J. Chem. Soc. 71(1897), 1076).

Formula (XIV) provides a general definition of the malonic estersrequired as reaction components in carrying out process (e). In thisformula R⁹ and R¹⁰ preferably have those meanings which have alreadybeen mentioned as preferred for these radicals in connection with thedescription of the malonic ester derivatives of the formula (XI).

The malonic esters of the formula (XIV) are known or can be prepared byknown methods.

Diluents which can be employed in carrying out process (e) are allcustomary inert organic solvents. Those which can be preferably used arepolar, aprotic solvents, such as ethers, such as dioxane,tetrahydrofuran or 1,2-dimethoxyethane, further amides, such asN,N-dimethylformamide, N,N-dimethylacetamide or N-methyl-pyrrolidone,furthermore nitriles, such as acetonitrile, propionitrile,n-butyronitrile or iso-butyronitrile, additionally sulphoxides, such asdimethyl sulphoxide, and also sulphones, such as sulpholane.

Acid-binding agents which can be employed in carrying out process (e)are all acid acceptors customary for reactions of this type. Those whichcan be preferably used are tertiary amines, such as trimethylamine,triethylamine, tributylamine, N,N-dimethylaniline,N,N-dimethyl-benzylamine, pyridine, N-methylpyridine,N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).

Suitable catalysts in carrying out process (e) are all reactionaccelerators customary for reactions of this type. Those which can bepreferably used are salts of polyvalent metals, such as magnesiumchloride, zinc chloride, copper (II) sulphate or iron (III) chloride.

The reaction temperatures can be varied within a certain range incarrying out process (e). The reaction is in general carried out attemperatures between -20° C. and +40° C., preferably between -10° C. and+30° C.

Both process (e) and processes (c) and (d) are in general carried outunder atmospheric pressure. However, it is also possible to carry outeach of the processes under increased or reduced pressure.

In carrying out process (e), in general 0.5 to 2 mol, preferably 0.8 to1.5 mol, of malonic ester of the formula (XIV) are employed per mole ofisonicotinoyl halide of the formula (XII). Working up is carried out bycustomary methods. A procedure is in general used in which the reactionis acidified, the mixture obtained in this way is extracted with apoorly water-miscible organic solvent, and the combined organic phasesare washed, optionally dried, and concentrated. The residual productscan optionally be freed by customary methods from impurities which maypossibly be present.

Possible diluents when carrying out process (d) are preferablywater-miscible, organic solvents. Examples which may be mentioned aretetrahydrofuran, acetonitrile, dimethyl sulphoxide and sulpholane.

The reaction temperatures can be varied within a substantial range incarrying out process (d). The reaction is in general carried out attemperatures between 50° C. and 200° C., preferably between 80° C. and180° C.

In carrying out process (d), in general 2 to 5 mol, preferably 2 to 2.5mol, of water are employed per mole of malonic ester derivative of theformula (XI). Working up is carried out by customary methods. Aprocedure is in general used in which ice-water is added to thereaction, the resulting mixture is extracted several times with a poorlywater-miscible organic solvent, the combined organic phases are washedwith water in the presence of a base, then dried and concentrated, andthe residue which remains is distilled.

Possible halogenating agents in carrying out process (c) are preferablybromine, chlorine, N-bromo-succinimide or N-iodo-succinimide.

Diluents which can be employed in carrying out process (c) are allcustomary inert, organic solvents. Those which can preferably be usedare optionally halogenated aliphatic, alicyclic or aromatichydrocarbons, such as hexane, cyclohexane, benzene, dichloromethane,chloroform, tetrachloromethane or trichloroethane.

Possible catalysts in carrying out process (c) are preferably Lewisacids, such as aluminium trichloride.

The reaction temperatures can also be varied within a substantial rangein carrying out process (c). The reaction is in general carried out attemperatures between -20° C. and +120° C., preferably between 10° C. and50° C.

In carrying out process (c), in general 0.5 to 5 mol, preferably 0.8 to1.2 mol, of halogenating agent are employed per mole of acetylpyridineof the formula (X).

Working up is carried out by customary methods. A procedure is ingeneral used in which water is added to the reaction mixture, theorganic phase is washed successively with water in the presence of thebase and then with water, subsequently dried and concentrated. Theproduct obtained can be freed by customary methods from impurities whichmay possibly still be present.

Formula (III) provides a general definition of the thio compoundsfurthermore required as starting substances for carrying out process (a)according to the invention. In this formula (III), R preferably hasthose meanings which have already been mentioned as preferred for R inconnection with the description of the compounds of the formula (I)according to the invention.

The thio compounds of the formula (III) are known synthesis chemicals.

The aminothiazoles of the formula (Ia) required as starting substancesfor carrying out process (b) according to the invention are substancesaccording to the invention which can be prepared by process (a)according to the invention.

The formulae (IV) and (V) provide general definitions of the carboxylicanhydrides required as reaction components in carrying out process (b,variant α) according to the invention.

In these formulae, R⁵ and A preferably have those meanings which havealready been mentioned as preferred for these radicals in connectionwith the description of the pyridyl-thiazoles of the formula (I)according to the invention.

The carboxylic anhydrides of the formulae (IV) and (V) are known or canbe prepared by known processes.

Formula (VI) provides a general definition of the carboxylic halidesrequired as reaction components in carrying out process (b, variant β)according to the invention. In this formula, R⁵ preferably has thosemeanings which have already been mentioned as preferred for this radicalin connection with the description of the pyridyl-thiazoles according tothe invention. X⁴ preferably represents chlorine or bromine.

The carboxylic halides of the formula (VI) are known or can be preparedby known processes.

The formula (VII) provides a general definition of the isocyanatesrequired as reaction components in carrying out process (b, variant γ)according to the invention. In this formula, R⁷ preferably representsstraight-chain or branched alkyl having 1 to 6 carbon atoms, aryl having6 to 10 carbon atoms or aryl-sulphonyl having 6 to 10 carbon atoms, itbeing possible for each of the two latter radicals to be mono- totrisubstituted in the aryl part in an identical or different manner byhalogen, cyano, nitro, formyl, carboxyl, carbamoyl, alkyl having 1 to 6carbon atoms, alkoxy having 1 to 6 carbon atoms, alkylthio having 1 to 6carbon atoms, alkylsulphinyl having 1 to 4 carbon atoms, alkylsulphonylhaving 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and1 to 5 fluorine, chlorine and/or bromine atoms, halogenoalkoxy having 1to 4 carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms,halogenoalkylthio having 1 to 4 carbon atoms and 1 to 5 fluorine,chlorine and/or bromine atoms, halogenoalkylsulphinyl having 1 to 4carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms,halogenoalkylsulphonyl having 1 to 4 carbon atoms and 1 to 5 fluorine,chlorine and/or bromine atoms, alkoxycarbonyl having 1 to 4 carbon atomsin the alkoxy part, hydroximinoalkyl having 1 to 4 carbon atoms in thealkyl part, alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxypart and 1 to 4 carbon atoms in the alkyl part and/or divalentalkanediyl having 3 or 4 carbon atoms, in which one or two(non-adjacent) carbon atoms can be replaced by oxygen and in which thealkanediyl part can be mono- to tetrasubstituted in an identical ordifferent manner by halogen, alkyl having 1 to 4 carbon atoms and/orhalogenoalkyl having 1 or 2 carbon atoms and 1 to 3 fluorine, chlorineand/or bromine atoms.

R⁷ particularly preferably represents methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, phenyl, naphthyl,phenylsulphonyl or naphthylsulphonyl, it being possible for each of thefour latter radicals to be mono- to trisubstituted in the aryl part inan identical or different manner by fluorine, chlorine, bromine, cyano,nitro, formyl, carboxyl, carbamoyl, methyl, ethyl, n- or i-propyl, n-,i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, methylthio,ethylthio, n- or i-propylthio, methylsulphinyl ethylsulphinyl,methylsulphonyl or ethylsulphonyl, trifluoromethyl, trifluoroethyl,difluoromethoxy, trifluoromethoxy, difluorochloromethoxy,trifluoroethoxy, difluoromethylthio, difluorochloromethylthio,trifluoromethylthio, trifluoromethylsulphinyl ortrifluoromethylsulphonyl, methoxycarbonyl, hydroximinomethyl,hydroximinoethyl, methoximinomethyl, ethoximinomethyl, methoximinoethylor ethoximinoethyl and/or in each case divalent trimethylene(propane-1,3-diyl), methylenedioxy or ethylenedioxy, which are in eachcase optionally mono- to tetrasubstituted in an identical or differentmanner by fluorine, chlorine, methyl, trifluoromethyl, ethyl or n- or1-propyl.

The isocyanates of the formula (VII) are known or can be prepared byknown processes.

Formula (VIII) provides a general definition of the acetals required asreaction components in carrying out process (b, variant δ) according tothe invention. In this formula, R³ and R⁴ preferably have those meaningswhich have already been mentioned as preferred for these radicals inconnection with the description of the pyridyl-thiazoles of the formula(I) according to the invention. R⁸ preferably represents methyl orethyl.

Possible diluents in carrying out the process (a) according to theinvention are all the customary inert organic solvents. Solvents whichcan preferably be used are aliphatic, alicyclic or aromatichydrocarbons, such as, for example, petroleum ether, hexane, heptane,cyclohexane, methylcyclohexane, benzene, toluene, xylene or Decalin;halogenated hydrocarbons, such as, for example, chlorobenzene,dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride,dichloroethane or trichloroethane; ethers, such as diethyl ether,diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane,tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole;ketones, such as acetone, butanone, methyl isobutyl ketone orcyclohexanone; nitriles, such as acetonitrile, propionitrile, n- ori-butyronitrile or benzonitrile; amides, such as N,N-dimethylformamide,N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone orhexamethylphosphoric triamide; esters, such as methyl acetate or ethylacetate; sulphoxides, such as dimethyl sulphoxide; and sulphones such assulpholane.

Possible acid-binding agents in carrying out process (a) according tothe invention are all the customary inorganic or organic bases. Baseswhich can preferably be used are alkaline earth metal or alkali metalhydrides, hydroxides, amides, alcoholates, acetates, carbonates, orbicarbonates, such as, for example, sodium hydride, sodium amide, sodiummethylate, sodium ethylate, potassium tert-butylate, sodium hydroxide,potassium hydroxide, sodium acetate, potassium acetate, calcium acetate,sodium carbonate, potassium carbonate, potassium bicarbonate or sodiumbicarbonate, and furthermore ammonium compounds, such as ammoniumhydroxide, ammonium acetate and ammonium carbonate, and in additiontertiary amines, such as trimethylamine, triethylamine, tributylamine,N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyridine,N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine,diazabicyclooctane (DABCO), diazabicyclononene (DBN) ordiazabicycloundecene (DBU).

However, it is also possible to carry out process (a) according to theinvention in the absence of additional acid-binding agents.

The reaction temperatures can be varied within a substantial range incarrying out process (a) according to the invention. The reaction is ingeneral carried out at temperatures between -20° C. and +100° C.,preferably between 0° C. and 80° C.

Both process (a) according to the invention and process (b) are ingeneral carried out under normal pressure. However, it is also possibleto carry out each of the processes under increased or reduced pressure,for example between 0.1 bar and 10 bar.

In carrying out process (a) according to the invention, in general 0.8to 10 mol, preferably 1 to 5 mol, of thio compound of the formula (III)are employed per mole of halogenoacetyl-pyridine of the formula (II).Working up is carried out by customary methods.

Possible diluents in carrying out process (b) according to the inventionare all the customary inert organic solvents. Solvents which canpreferably be used in the case of variants (α), (β) and (γ) are allthose solvents which have already been mentioned as preferred in thecase of process (a) according to the invention. Alcohols, such asmethanol or ethanol, can also be employed as diluents for carrying outvariant (δ).

Possible acid-binding agents for carrying out process (b), variants αand β, according to the invention are all the acid acceptors customaryfor such reactions. Acid acceptors which can preferably be used here arethose acid-binding agents which have already been mentioned as preferredin the case of process (a) according to the invention.

Separate addition of a catalyst is in general unnecessary for carryingout variants (α) and (β) of process (b) according to the invention.

The addition of an acid-binding agent is in general not necessary forcarrying out variants (γ) and (δ) of process (b) according to theinvention.

Possible catalysts for carrying out variant (γ) of process (b) accordingto the invention are all the reaction accelerators customary for suchreactions. Reaction accelerators which can preferably be used areamines, such as pyridine, dimethylaminopyridine anddiazabicyclo-undecene (DBU).

Possible catalysts for carrying out variant (δ) of process (b) accordingto the invention are all the reaction accelerators customary for suchreactions. Reaction accelerators which can preferably be used are acids,such as sulphuric acid, hydrochloric acid and toluenesulphonic acid, andfurthermore also acid ion exchangers.

The reaction temperatures can also be varied within a substantial rangewhen carrying out process (b) according to the invention. The reactionis in general carried out at temperatures between 0° C. and 150° C.,preferably between 10° C. and 120° C.

In carrying out process (b) according to the invention, in general 0.8to 15 mol, preferably 1 to 8 mol, of reaction component of the formula(IV), (V), (VI), (VII) or (VIII) are employed per mole of aminothiazoleof the formula (Ia). Working up is carried out by customary methods.

For preparation of salts of compounds according to the invention, aprocedure is in general followed in which a pyridyl-thiazole of theformula (Ib) is dissolved in an inert organic solvent, such as, forexample, methanol or ethanol, and a strong base of the formula (IX) isadded at room temperature or also at somewhat elevated temperature.Isolation and any purification required for the salts formed by thisreaction are carried out by customary methods.

The pyridyl-thiazoles of the formula (I) according to the invention canalso be converted into acid addition salts.

Possible acids for preparation of acid addition salts of the compoundsof the formula (I) are preferably those acids which have already beenmentioned as preferred acids in connection with the description of theacid addition salts according to the invention.

The acid addition salts of the compounds of the formula (I) can beobtained in a simple manner by customary salt formation methods, forexample by dissolving a compound of the formula (I) in a suitable inertsolvent and adding the acid, for example hydrochloric acid, and they canbe isolated in a known manner, for example by filtration, and ifappropriate purified by washing with an inert organic solvent.

The active compounds according to the invention have a potentresistance-inducing action in plants. They are therefore suitable forgenerating resistance in plants against attack by undesirablemicroorganisms.

Resistance-inducing substances in the present connection are to beunderstood as those substances which are capable of stimulating thedefence system of plants such that the treated plants, when subsequentlyinoculated with undesirable microorganisms, display substantialresistance to these microorganisms.

Undesirable microorganisms in the present case are to be understood asphytopathogenic fungi, bacteria and viruses. The substances according tothe invention can thus be employed to generate resistance in plantsagainst attack by the harmful organisms mentioned within a certainperiod of time after the treatment. The period of time within whichresistance is brought about in general extends from 1 to 10 days,preferably 1 to 7 days, after treatment of the plants with the activecompounds.

In addition to the resistance-inducing action, the active compoundsaccording to the invention also have a potent microbicidal action andare also employed in practice for directly combating undesirablemicroorganisms. The active compounds are suitable for use as plantprotection agents, in particular as fungicides.

Undesirable microorganisms in plant protection include fungi from theclasses Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes,Ascomycetes, Basidiomycetes and Deuteromycetes.

Some causative organisms of fungal diseases which come under the genericnames listed above may be mentioned as examples, but not by way oflimitation:

Pythium species, such as, for example, Pythium ultimum;

Phytophthora species, such as, for example, Phytophthora infestans;

Pseudoperonospora species, such as, for example, Pseudoperonosporahumuli or Pseudoperonospora cubensis,

Plasmopara species, such as, for example, Plasmopara viticola;

Peronospora species, such as, for example, Peronospora pisi orPeronospora brassicae;

Erysiphe species, such as, for example, Erysiphe graminis;

Sphaerotheca species, such as, for example, Sphaerotheca fuliginea;

Podosphaera species, such as, for example, Podosphaera leucotricha;

Venturia species, such as, for example, Venturia inaequalis;

Pyrenophora species, such as, for example, Pyrenophora teres orPyrenophora graminea (conidia form: Drechslera, syn: Helminthosporium);

Cochliobolus species, such as, for example, Cochliobolus sativus(conidia form: Drechslera, syn: Helminthosporium);

Uromyces species, such as, for example, Uromyces appendiculatus;

Puccinia species, such as, for example, Puccinia recondita;

Tilletia species, such as, for example, Tilletia caries;

Ustilago species, such as, for example, Ustilago nuda or Ustilagoavenae;

Pellicularia species, such as, for example, Pellicularia sasakii;

Pyricularia species, such as, for example, Pyricularia oryzae;

Fusarium species, such as, for example, Fusarium culmorum;

Botrytis species, such as, for example, Botrytis cinerea;

Septoria species, such as, for example, Septoria nodorum,

Leptosphaeria species, such as, for example, Leptosphaeria nodorum;

Cercospora species, such as, for example, Cercospora canescens;

Alternaria species, such as, for example, Alternaria brassicae and

Pseudocercosporella species, such as, for example, Pseudocercosporellaherpotrichoi des.

The good toleration, by plants, of the active compounds, at theconcentrations required for combating plant diseases, permits treatmentof above-ground parts of plants, and also treatment of vegetativepropagation stock and seeds, and of the soil.

The active compounds according to the invention can also be used withparticularly good success for combating cereal diseases, such as, forexample, against Erysiphe species, or diseases in wine, fruit andvegetable growing, such as, for example, against Plasmopara or Venturiaspecies, or rice diseases, such as, for example, against Pyriculariaspecies. Other plant diseases, such as, for example, Septoria,Cochliobolus, Pyrenophora and Pseudocercosporella species, can also becombated with good success with the active compounds according to theinvention.

Depending on their particular physical and/or chemical properties, theactive compounds can be converted into the customary formulations, suchas solutions, emulsions, suspensions, powders, foams, pastes, granules,aerosols, very fine capsules in polymeric substances and in coatingcompositions for seed, as well as ULV cold-mist and warm-mistformulations.

These formulations are produced in a known manner, for example by mixingthe active compounds with extenders, that is, liquid solvents, liquefiedgases under pressure, and/or solid carriers, optionally with the use ofsurface-active agents, that is, emulsifying agents and/or dispersingagents, and/or foam-forming agents. In the case of the use of water asan extender, organic solvents can, for example, also be used asauxiliary solvents. As liquid solvents, there are suitable in the main:aromatics, such as xylene, toluene or alkylnaphthalenes, chlorinatedaromatics or chlorinated aliphatic hydrocarbons, such as chlorobenzenes,chloroethylenes or methylene chloride, aliphatic hydrocarbons, such ascyclohexane or paraffins, for example mineral oil fractions, alcohols,such as butanol or glycol as well as their ethers and esters, ketones,such as acetone, methyl ethyl ketone, methyl isobutyl ketone orcyclohexanone, strongly polar solvents, such as dimethylformamide anddimethyl sulphoxide, as well as water; by liquefied gaseous extenders orcarriers are meant liquids which are gaseous at ambient temperature andunder atmospheric pressure, for example aerosol propellants, such ashalogenated hydrocarbons as well as butane, propane, nitrogen and carbondioxide; as solid carriers there are suitable: for example groundnatural minerals, such as kaolins, clays, talc, chalk, quartz,attapulgite, montmorillonite or diatomaceous earth, and ground syntheticminerals, such as highly disperse silica, alumina and silicates; assolid carriers for granules there are suitable: for example crushed andfractionated natural rocks such as calcite, marble, pumice, sepioliteand dolomite, as well as synthetic granules of inorganic and organicmeals, and granules of organic material such as sawdust, coconut shells,maize cobs and tobacco stalks; as emulsifying and/or foam-forming agentsthere are suitable: for example non-ionic and anionic emulsifiers, suchas polyoxyethylene fatty acid esters, polyoxyethylene fatty alcoholethers, for example alkylaryl polyglycol ethers, alkylsulphonates, alkylsulphates, arylsulphonates as well as albumen hydrolysis products, asdispersing agents there are suitable: for example lignin-sulphite wasteliquors and methylcellulose.

Adhesives such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latices, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, as well as naturalphospholipids, such as cephalins and lecithins, and syntheticphospholipids, can be used in the formulations. Other additives can bemineral and vegetable oils.

It is possible to use colorants such as inorganic pigments, for exampleiron oxide, titanium oxide and Prussian Blue, and organic dyes, such asalizarin dyes, azo dyes and metal phthalocyanine dyes, and tracenutrients such as salts of iron, manganese, boron, copper, cobalt,molybdenum and zinc.

The formulations in general contain between 0.1 and 95 per cent byweight of active compound, preferably between 0.5 and 90%.

The active compounds according to the invention can also be used as suchor in their formulations as a mixture with known fungicides,bactericides, acaracides, nematicides or insecticides, in order thus,for example, to widen the action spectrum or prevent development ofresistances.

Synergistic actions are observed in many cases in these mixtures.

Possible components for the mixtures are, for example:

Fungicides:

2-aminobutane; 2-anilino-4-methyl-6-cyclopropyl-pyrimidine;2',6'-dibromo-2-methyl-4'-trifluoromethoxy-4'-trifluoro-methyl-1,3-thiazole-5-carboxanilide;2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide;(E)-2-methoximino-N-methyl-2-(2-phenoxy-phenyl)-acetamide;8-hydroxyquinoline sulphate; methyl(E)-2-{2-[6-(2-cyano-phenoxy)-pyrimidine-4-yloxy]-phenyl}-3-methoxyacrylate;methyl (E)-methox-imino[alpha-(o-tolyloxy)o-tolyl]acetate; 2-phenylphenol (OPP), aldimorph, ampropylfos, anilazine, azaconazole,

benalaxyl, benodanil, benomyl, binapacryl, biphenyl, bitertanol,blasticidin-S, bromuconazole, bupirimate, buthiobate, calciumpolysulphide, captafol, captan, carbendazim, carboxin, chinomethionat(quinomethionate), chloroneb, chloropicrin, chlorothalonil, chlozolinat,cufraneb,

cymoxanil, cyproconazole, cyprofuram,

dichlorophene, dichlobutrazole, diclofluanid, diclomezin, dichloran,diethofencarb,

difenoconazole, dimethirimol, dimethomorph, diniconazole, dinocap,diphenylamine, dipyrithione, ditalimfos, dithianon, dodine, drazoxolon,

edifenphos, epoxyconazole, ethirimol, etridiazole,

fenarimol, fenbuconazole, fenfuram, fenitropan, fenpiclonil,fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam,ferimzone, fluazinam, fludioxonil, fluoromide, fluquinconazole,flusilazole, flusulphamide, flutoanil, flutriafol, folpet,fosetyl-aluminium, fthalide, fuberidazole, furalaxyl, furmecyclox,

guazatine,

hexachlorobenzene, hexaconazole, hymexazole,

imazalil, imibenconazole, iminoactadin, iprobenfos (IBF), iprodione,isoprothiolan,

kasugamycin, copper formulations, such as: copper hydroxide, coppernaphthenate, copper oxychloride, copper sulphate, copper oxide,oxine-copper and Bordeaux mixture,

mancopper, mancozeb, mepanipyrim, mepronil, metalaxyl, metconazole,

methasulphocarb, methfuroxam, metiram, metsulphovax, myclobutanil,

nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol,

ofurace, oxadixyl, oxamocarb, oxycarboxin,

perfurazoat, penconazole, pencycuron, phosdiphen, pimaricin, piperalin,polyoxin, probenazole, prochloraz, procymidon, propamocarb,propiconazole, propineb, pyrazophos, pyrifenox, pyrimethanil,pyroquilone

quintozene (PCNB),

sulphur and sulphur formulations,

tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole,thicyofen, thiophanate-methyl, thiram, tolclophos-methyl, tolylfluanid,triadimefon, triadimenol, triazoxid, trichlamid, tricyclazole,tridemorph, triflumizole, triforine, triticonazole,

validamycin A, vinclozolin,

zineb, ziram

Bactericides:

bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate,kasugamycin, octhilinon, furancarboxylic acid, oxytetracycline,probenazole, streptomycin, tecloftalam, copper sulphate and other copperformulations.

Insecticides/Acaricides/Nematicides:

abamectin, AC₃₀₃ 630, acephate, acrinathrin, alanycarb, aldicarb,alphamethrin, amitraz, avermectin AZ 60541, azadirachtin, azinphos A,azinphos M, azocyclotin,

Bacillus thuringiensis, bendiocarb, benfuracarb, bensultap,betacyfluthrin, bifenthrin, BPMC, brofenprox, bromophos A, bufencarb,buprofezin, butocarboxim, butylpyridaben,

cadusafos, carbaryl, carbofuran, carbophenothion, carbosulphan, cartap,CGA 157 419, CGA 184699, chloethocarb, chlorethoxyfos, chlorfenvinphos,chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos M,cis-resmethrin,

clocythrin, clofentezin, cyanophos, cycloprothin, cyfluthrin,cyhalothrin, cyhexatin, cypermethrin, cyromazin,

deltamethrin, demeton M, demeton S, demeton--S--methyl, diafenthiuron,diazinon, dichlofenthion, dichlorvos, dicliphos, dicrotophos, diethion,diflubenzuron, dimethoate, dimethylvinphos, dioxathion, disulphoton,

edifenphos, emamectin, esfenvalerate, ethiofencarb, ethion, ethofenprox,ethoprophos, etrimphos,

fenamiphos, fenazaquin, fenbutatin oxide, fenitrothion, fenobucarb,fenothiocarb,

fenoxycarb, fenpropathrin, fenpyrad, fenpyroximate, fenthion,fenvalerate,

fipronil, fluazinam, flucycloxuron, flucythrinate, flufenoxuron,flufenprox, fluvalinate, fonophos, formothion, fosthiazate, fubfenprox,furathiocarb,

HCH, heptenophos, hexaflumuron, hexythiazox,

imidacloprid, iprobenfos, isazophos, isofenphos, isoprocarb, isoxathion,ivermectin,

lambda-cyhalothrin, lufenuron,

malathion, mecarbam, mevinphos, mesulphenphos, metaldehyde, methacrifos,

methamidophos, methidathion, methiocarb, methomyl, metolcarb,milbemectin,

monocrotophos, moxidectin,

naled, NC₁₈₄, NI 25, nitenpyram

omethoate, oxamyl, oxydemethon M, oxydeprofos,

parathion A, parathion M, permethrin, phenthoate, phorate, phosalone,phosmet,

phosphamidon, phoxim, pirimicarb, pirimiphos M, pirimiphos A,

profenophos, promecarb, propaphos, propoxur, prothiofos, prothiophos,prothoate,

pymetrozin, pyrachlophos, pyridaphenthion, pyresmethrin, pyrethrum,pyridaben, pyrimidifen pyriproxifen,

quinalphos,

RH 5992,

salithion, sebufos, silafluofen, sulphotep, sulprofos,

tebufenozide, tebufenpyrad, tebupirimiphos, teflubenzuron, tefluthrin,temephos, terbam, terbufos, tetrachlorvinphos, thiafenox, thiodicarb,thiofanox, thiomethon, thionazin, thuringiensin, tralomethrin,triarathen, triazophos, triazuron, trichlorfon, triflumuron,trimethacarb,

vamidothion, XMC, xylylcarb, zetamethrin.

The active compounds according to the invention can also be mixed withother known active compounds, such as herbicides, or also withfertilizers and growth regulators.

The active compounds can be used as such or in the form of theirformulations or the use forms prepared therefrom, such as ready-to-usesolutions, suspensions, wettable powders, pastes, soluble powders, dustsand granules. They are used in the customary manner, for example bywatering, spraying, atomizing, scattering, dusting, foaming, brushing onand the like. It is furthermore possible to apply the active compoundsby the ultra-low volume method or to inject the active compoundformulation or the active compound itself into the soil. The seeds ofthe plants can also be treated.

In the treatment of parts of plants, the active compound concentrationsin the use forms can be varied within a substantial range: they are, ingeneral, between 1 and 0.0001% by weight, preferably between 0.5 and0.001% by weight.

In the treatment of seed, amounts of active compound of 0.001 to 50 gper kilogram of seed, preferably 0.01 to 10 g, are generally required.

For the treatment of soil, active compound concentrations of 0.00001 to0.1% by weight, preferably 0.0001 to 0.02% by weight, are required atthe place of action.

The preparation and the use of active compounds according to theinvention are illustrated by the following examples.

PREPARATION EXAMPLES Example 1 ##STR33##

931.5 g (3.46 mol) of 4-bromoacetyl-2,6-dichloropyridine and 318.2 g(4.18 mol) of thiourea are brought together in 4.2 liters of acetone,stirring, during which the temperature rises to 45° C. The mixture isstirred for a further 3 hours. The solid obtained by this procedure isfiltered off with suction, washed with a little acetone and dried whilefurther filtering with suction. The product thus obtained is suspendedin 2 liters of water at room temperature, a pH of 10 is established byaddition of concentrated aqueous sodium hydroxide solution, and thesolid is filtered off with suction again, rinsed with 3 liters of waterand dried at 50° C. under reduced pressure. The crude product thusobtained is stirred with 30 liters of tert-amyl methyl ether and themixture obtained by this procedure is filtered with suction. Thefiltrate is concentrated under reduced pressure and the residue whichremains is dried at 50° C. under reduced pressure. The solid isolatedafter the tert-amyl methyl ether mixture has been filtered with suctionis dissolved in 1 liter of hot ethanol. The solution formed is filteredand the filtrate is then cooled to 5° C. The solid which precipitates inthis procedure is also filtered off with suction and dried at 50° C.under reduced pressure. A total of 600.1 g (70.5% of theory) of[4-(2,6-dichloropyridin-4-yl)-thiazol-2-yl]-amine are obtained in thismanner as a solid substance of melting point 239 to 247° C.

Preparation of starting substances: ##STR34##

First 2 g of aluminium chloride are added to a solution of 525 g (2.763mol) of 4-acetyl-2,6-dichloro-pyridine in 1.37 liters of dichloromethaneand then 417.6 g (2.613 mol) of bromine are added dropwise with stirringat 30 to 35° C. in the course of 30 minutes. After addition is complete,the reaction mixture is subsequently stirred for a further hour at 35°C. and 1.2 l of water are then added. The organic phase is separated offand washed successively, first with 1.2 l of saturated, aqueous sodiumhydrogen carbonate solution and then twice with 1.2 l of water eachtime. It is dried over sodium sulphate and then concentrated underreduced pressure. The residue which remains is stirred with 2 l ofpetroleum ether, then filtered off with suction and washed in portionswith a total of 1 liter of petroleum ether. The product obtained isdried at 50° C. under reduced pressure. In this manner 592.2 g (79.7% oftheory) of 4-bromo-acetyl-2,6-dichloro-pyridine are obtained in the formof a solid substance.

¹ H-NMR spectrum (CDCl₃ /TMS): δ=4.42 (s, 2H); 7.74 (s, 2H) ppm##STR35##

1328 g (4.34 mol) of dimethyl 2,6-dichloro-isonicotinoyl-malonate aredissolved in a mixture of 3.45 l of dimethyl sulphoxide and 156.2 g(8.68 mol) of water. The reaction mixture is heated to 140° C. andstirred at this temperature for 30 minutes. After this, the reactionmixture is cooled to 10° C. and then added to 8.4 l of ice-water. Themixture is extracted twice with a total of 3.6 l of dichloromethane andthe combined organic phases are washed once with 1.5 l of saturated,aqueous sodium hydrogen carbonate solution. After drying over sodiumsulphate, the organic phase is concentrated under reduced pressure. Theresidue which remains is distilled under reduced pressure. In thismanner 506.0 g (60% of theory) of 4-acetyl-2,6-dichloropyridine ofboiling point 98° C. at 0.5 mbar are obtained. ##STR36##

2312 g (24.28 mol) of magnesium chloride are introduced with coolinginto 18 l of acetonitrile. After the exothermic reaction has subsided,the solution is cooled to 0° C. and 3210 g (24.3 mol) of dimethylmalonate are added dropwise with stirring in the course of 45 minutes.After this, 4920 g (48.62 mol) of triethylamine are added dropwise at 0°C. with stirring in the course of 1.5 hours. After addition is complete,the mixture is stirred at 0° C. for a further 15 minutes. A solution of4742 g (22.53 mol) of 2,6-dichloro-isonicotinyl chloride in 6670 ml ofacetonitrile is then added dropwise at 0° C. with stirring in the courseof 20 hours. The mixture is first stirred for 1 hour at 0° C. and thenfor 16 hours while slowly warming to room temperature. 15.9 l ofconcentrated hydrochloric acid are then added dropwise with stirring tothe reaction mixture with cooling to 0 to 10° C. After this, 15.9 l ofdichloromethane and 6.4 l of water are added with stirring and theorganic phase is then separated off. The aqueous phase is extracted oncemore with 7.9 l of dichloromethane. The combined organic phases arewashed twice with 4 l of water each time and then concentrated underreduced pressure. The residue which remains is stirred with 9.5 l ofwater, then filtered off with suction and washed successively, firstwith 6.3 l of water and then twice with 7.9 l of petroleum ether eachtime. The product obtained is dried at 40° C. under reduced pressure. Inthis manner, 6.17 kg (89.2% of theory) of dimethyl2,6-dichloro-isonicotinoyl-malonate are obtained.

¹ H-NMR spectrum (CDCl₃ /TMS): δ=3.68; 3.84; 3.92 and 7.39 ppm.

Example 2 ##STR37##

7.53 g (0.03 mol) of 2-trifluoromethylphenylsulphonyl isocyanate areadded to a solution of 7.38 g (0.03 mol) of[4-(2,6-dichloropyridin-4-yl)-thiazol-2-yl]-amine in 180 ml ofacetonitrile at 75° C. in the course of 5 minutes, while stirring. Thereaction mixture is stirred at 75° C. for a further 3 hours and thencooled to room temperature, and the solid which has precipitated out isfiltered off with suction, washed twice with 10 ml of acetonitrile eachtime and dried at 45° C. under reduced pressure. 14 g (93.9% of theory)ofN-[4-(2,6-dichloro-pyridin-4-yl)-thiazol-2-yl]-N'-(2-trifluoromethyl-phenylsulphonyl)-ureaare obtained in this manner in the form of a solid substance with amelting point of >280° C.

Example 3 ##STR38##

7.38 g (0.03 mol) of [4-(2,6-dichloropyridin-4-yl)-thiazol-2-yl]-amineand 70 ml of acetic anhydride are heated under reflux for 30 minutes, asolution initially forming but a precipitate then separating out. Thereaction mixture is left to stand at room temperature for 16 hours, 200ml of ice-water are then added and the mixture is filtered with suction.The residue is first washed several times with water and then digestedwith 200 ml of 5% strength aqueous sodium bicarbonate solution, and isfiltered off with suction again. The product is dried at 50° C. underreduced pressure. 8.1 g (93.8% of theory) ofN-[4-(2,6-dichloropyridin-4-yl)-thiazol-2-yl]-acetamide are obtained inthis manner in the form of a solid substance of melting point 301° C.

Example 4 ##STR39##

3.93 g (0.033 mol) of dimethylformamide dimethyl acetal are added to amixture of 7.38 g (0.03 mol) of[4-(2,6-dichloropyridin-4-yl)-thiazol-2-yl]-amine and 50 ml of methanolat 20° C., while stirring, and the mixture is stirred at 50° C. for afurther 2 hours. Thereafter, the reaction mixture is cooled to 10° C.and filtered with suction. The residue is washed with 10 ml of coldmethanol and then dried at 45° C. under reduced pressure. 7.5 g (83% oftheory) ofN-[4-(2,6-dichloropyridin-4-yl)-thiazol-2-yl]-N,N'-dimethylformamidineare obtained in this manner in the form of a solid substance of meltingpoint 145° C.

The compounds of the formula ##STR40## listed in the following table arealso prepared by the methods described above.

                  TABLE 1                                                         ______________________________________                                        Ex.                                  Melting                                  No.  X.sup.1                                                                             X.sup.2                                                                             R                   point (° C.)                      ______________________________________                                        5    Cl    Cl    --CH.sub.3          131-133                                  6    Cl    Cl                                                                                   ##STR41##          278                                      7    Cl    Cl                                                                                   ##STR42##          300 (decom-  position)                   8    Cl    Cl                                                                                   ##STR43##          168 (decom-  position)                   9    Cl    Cl    --NH--CO--CO--OC.sub.2 H.sub.5                                                                    163                                      ______________________________________                                    

USE EXAMPLES Example A

Plasmopara test (vines) protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound until dew-moist. After the spray coatinghas dried on, the plants are inoculated with an aqueous spore suspensionof Plasmopara viticola and then remain in a humidity chamber at 20 to22° C. and 100% relative atmospheric humidity for 1 day. The plants arethen placed in a greenhouse at 21° C. and about 90% atmospheric humidityfor 5 days. The plants are then moistened and placed in a humiditychamber for 1 day.

Evaluation is carried out 6 days after the inoculation. In thisevaluation, 0% denotes a degree of action which corresponds to that ofthe control, while a degree of action of 100% denotes that no attack isobserved.

The active compounds, active compound concentrations and test resultscan be seen from the following table.

                                      TABLE A                                     __________________________________________________________________________    Plasmopara test (vines)/protective                                                                        Degree of action in %, based on the                                           untreated control, at an active                                               compound concentration in the spray               Active compound             liquor of 100 ppm                                 __________________________________________________________________________    According to the invention:                                                    ##STR44##                  81                                                 ##STR45##                  85                                                __________________________________________________________________________

Example B

Venturia test (apple)/protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound until dripping wet. After the spraycoating has dried on, the plants are inoculated with an aqueous conidiasuspension of the apple scab causative organism Venturia inaequalis andthen remain in an incubation cabin at 20° C. and 100% relativeatmospheric humidity for 1 day.

The plants are then placed in a greenhouse at 20° C. and a relativeatmospheric humidity of about 70%.

Evaluation is carried out 12 days after the inoculation. In thisevaluation, 0% denotes a degree of action which corresponds to that ofthe control, while a degree of action of 100% denotes that no attack isobserved.

The active compound, active compound concentrations and test results canbe seen from the following table.

                                      TABLE B                                     __________________________________________________________________________    Venturia test (apple)/protective                                                                          Degree of action in %, based on the                                           untreated control, at an active                                               compound concentration in the spray               Active compound             liquor of 10 ppm                                  __________________________________________________________________________    According to the invention:                                                    ##STR46##                  76                                                 ##STR47##                  66                                                 ##STR48##                  72                                                __________________________________________________________________________

Example C

Erysiphe test (barley)/protective

Solvent: 10 parts by weight of N-methyl-pyrrolidone

Emulsifier: 0.6 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound at the stated application rate. After thespray coating has dried on, the plants are dusted with spores ofErysiphe graminis f.sp. hordei.

The plants are placed in a greenhouse at a temperature of about 20° C.and a relative atmospheric humidity of about 80%, in order to promotethe development of powdery mildew pustules.

Evaluation is carried out 7 days after the inoculation. In this, 0%denotes a degree of action which corresponds to that of the control,while a degree of action of 100% denotes that no attack is observed.

The active compounds, active compound concentrations and test resultscan be seen from the following table.

                  TABLE C                                                         ______________________________________                                        Erysiphe test (barley)/protective                                                               Degree of action in %, based on                                               the untreated control, at an                                                  amount of active                                            Active compound   compound applied of 250 g/ha                                ______________________________________                                        According to the invention:                                                    ##STR49##        77                                                          ______________________________________                                    

Example D

Erysiphe test (barley)/curative

Solvent: 10 parts by weight of N-methyl-pyrrolidone

Emulsifier: 0.6 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for curative activity, young plants are dusted with spores ofErysiphe graminis f. sp. hordei. 48 hours after the inoculation, theplants are sprayed with the preparation of active compound in the statedamount applied.

The plants are placed in a greenhouse at a temperature of about 20° C.and a relative atmospheric humidity of about 80%, in order to promotethe development of powdery mildew pustules.

Evaluation is carried out 7 days after the inoculation. In thisevaluation, 0% denotes a degree of action which corresponds to that ofthe control, while a degree of action of 100% denotes that no attack isobserved.

The active compounds, active compound concentrations and test resultscan be seen from the following table.

                  TABLE D                                                         ______________________________________                                        Erysiphe test (barley)/curative                                                                 Degree of action in %, based on                                               the untreated control, at an                                                  amount of active                                            Active compound   compound applied of 250 g/ha                                ______________________________________                                        According to the invention:                                                    ##STR50##        75                                                          ______________________________________                                    

Example E

Pyricularia test (rice)/protective

Solvent: 12.5 parts by weight of acetone

Emulsifier: 0.3 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent, and theconcentrate is diluted with water and the stated amount of emulsifier tothe desired concentration.

To test for protective activity, young rice plants are sprayed with thepreparation of active compound until dripping wet. 4 days after thespray coating has dried on, the plants are inoculated with an aqueousspore suspension of Pyricularia oryzae. The plants are then placed in agreenhouse at 100% relative atmospheric humidity and 25° C.

Evaluation of the disease infestation is carried out 4 days after theinoculation. In this evaluation, 0% denotes a degree of action whichcorresponds to that of the control, while a degree of action of 100%denotes that no attack is observed.

The active compounds, active compound concentrations and test resultscan be seen from the following table.

                  TABLE E                                                         ______________________________________                                        Pyricularia test (rice)/protective                                                                          Degree of                                                        Active compound                                                                            action in %,                                                     concentration in the                                                                       based on                                                         spray liquor in % by                                                                       the untreated                                   Active compound  weight       control                                         ______________________________________                                        According to the invention:                                                    ##STR51##       0,025        90                                              ______________________________________                                    

Example F

Pyricularia test (rice)/systemic

Solvent: 12.5 parts by weight of acetone

Emulsifier: 0.3 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent, and theconcentrate is diluted with water and the stated amount of emulsifier tothe desired concentration.

To test for systemic properties, 40 ml of the preparation of activecompound are poured onto standard soil, in which young rice plants havebeen grown. 7 days after the treatment, the plants are inoculated withan aqueous spore suspension of Pyricularia oryzae. The plants thenremain in a greenhouse at 100% relative atmospheric humidity and 25° C.until evaluation.

Evaluation of the disease infestation is carried out 4 days after theinoculation. In this, 0% denotes a degree of action which corresponds tothat of the control, while a degree of action of 100% denotes that noattack is observed.

The active compounds, active compound concentrations and test resultscan be seen from the following table.

                  TABLE F                                                         ______________________________________                                        Pyricularia test (rice)/systemic                                                               Amount                                                                        applied in                                                                    mg of active                                                                             Degree of action in                                                compound per                                                                             %, based on the                                   Active compound  100 cm.sup.2                                                                             untreated control                                 ______________________________________                                        According to the invention:                                                    ##STR52##       100        80                                                ______________________________________                                    

What is claimed is:
 1. A compound of the formula ##STR53## in which X²represents chlorine,X⁵ represents chlorine, R⁹ represents alkyl having 1to 4 carbon atoms and R¹⁰ represents alkyl having 1 to 4 carbon atoms.2. A compound dimethyl 2,6-dichloroisonicotinyl-malonate having thestructural formula ##STR54##
 3. A method for protecting plants againstattack by undesirable microorganisms, said method comprising applying tothe microorganisms or to their habitat an effective amount of a compoundaccording to claim 1.